A Multicenter Phase 3, Open-Label Study of Bosutinib Versus Imatinib in Adult Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia

A MULTICENTER PHASE 3 RANDOMIZED, OPEN-LABEL STUDY OF BOSUTINIB VERSUS IMATINIB IN ADULT PATIENTS WITH NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOGENOUS LEUKEMIA

Phase 3, 2-arm, randomized, open label trial. Patients will be randomized to receive bosutinib or imatinib for the duration of the study.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myelogenous, Chronic, Breakpoint Cluster Region-Abelson Proto-oncogene (BCR-ABL) Positive
• Intervention / Treatment: Drug: Bosutinib; Drug: Imatinib

Detailed Description

The study will be open for enrollment until the planned number of approximately 500 Philadelphia Chromosome Positive (Ph+) patients have been randomized (approximately 250 Ph+ patients in each treatment arm; a total of approximately 530 Ph+ and Ph- patients). All patients will be treated and/or followed for approximately 5 years (240 weeks) after randomization until the study has closed. Patients who discontinue study therapy early due to disease progression or intolerance to study medication will continue to be followed yearly for survival for up to approximately 5 years (240 weeks) after randomization.

• Study Type: Interventional
• Enrollment (Actual): 536
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital - Hematology Department
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Clinical Research Unit, Level 2
• Belgium
  • Ghent, Belgium, 9000
    • UZ Ghent (University Hospital Ghent)
  • Leuven, Belgium, 3000
    • Department of Haematology at UZ Leuven (7 th Floor)
  • Liège, Belgium, 4000
    • Hematology Department of CHU de Liège
  • Verviers, Belgium, 4800
    • Hematology Department CHR Verviers
• Canada
  • Quebec, Canada, G1J 1Z4
    • CHU de Québec - Université Laval
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Horizon Health Network - The Moncton Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Hôpital Maisonneuve-Rosemont
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno
  • Hradec Králové, Czechia, 500 05
    • Fakultní nemocnice Hradec Králové
  • Olomouc, Czechia, 775 20
    • Fakultní nemocnice Olomouc
  • Prague, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital
  • Roskilde, Denmark, 4000
    • Roskilde Hospital
• Finland
  • Helsinki, Finland, 00029 HUS
    • Helsinki University Central Hospital
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Le Chesnay, France, 78157
    • private Practice of Pr Philippe Rousselot
  • Nantes cedex 1, France, 44093
    • private Practice of Dr. Viviane Dubruille
  • Nice, France, 06202
    • Hôpital L'Archet 1-CHU Nice
  • Nimes, France, 30029
    • Institut de cancérologie du Gard - Hematologie clinique
  • Pierre Bénite, France, 69495
    • Pr Mauricette Michallet Centre Hospitalier Lyon Sud
  • Poitiers, France, 86021
    • INSERM CIC 1402 - CHU Poitiers
  • Toulouse cedex 9, France, 31059
    • Institut Universitaire du Cancer de Toulouse - Oncopole
  • NC
    • Strasbourg, NC, France, 67000
      • Oncologie Centre de Radiotherapie
• Germany
  • Aachen, Germany, 52074
    • Uniklinikum Aachen
  • Berlin, Germany, 13353
    • Charité, CVK, Med. Klinik m.S Hämatologie und Onkologie
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg, Klinik für Innere Medizin I
  • Hamburg, Germany, 20251
    • Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum
  • Jena Lobeda-Ost, Germany, 07747
    • Universitätsklinikum Jena, Klinik für Innere Medizin II
  • Magdeburg, Germany, 39104
    • Schwerpunktpraxis für Hämatologie und Onkologie
  • RP
    • Bonn, RP, Germany, 53105
      • Universitätsklinikum Bonn
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem I. Belgyógyászat
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Központ, Belgyógyászati Inézet Hematológiai Tanszék
  • Györ, Hungary, 9023
    • Petz Aladár Megyei OktatóKórház, II. Belgyógyászati Osztály és Haematológiai Részleg
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mór Oktató Kórház
  • Szeged, Hungary, 6725
    • Szegedi Tudományegyetem, AOK, Szent-Györgyi Albert Klinikai Központ, II. sz.
  • Szolnok, Hungary, 5000
    • Jász-Nagykun-Szolnok Megyei Hetényi, Géza Kórház-Rendelőintézet
• Israel
  • Haifa, Israel, 31096
    • Hematology Department, Rambam Medical Centre
  • Petah-Tikva, Israel, 49100
    • Hematology Div. Davidoff Cancer Center, Rabin Medical Center
• Italy
  • Bergamo, Italy, 24127
    • USC Ematologia, A. O. Papa Giovanni XXIII
  • Bologna, Italy, 40138
    • Policlinico S. Orsola - Malpighi,
  • Cagliari, Italy, 09121
    • A.O. Brozu - P.O. Armando Businco
  • Firenze, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi
  • Genova, Italy, 16132
    • IRCCS - AOU San Martino_IST, Ematologia 1
  • Milano, Italy, 20132
    • Istituto Scientifico San Raffaele
  • Monza, Italy, 20900
    • Unità di Ricerca Clinica, U.O. Ematologia Adulti
  • Napoli, Italy, 80131
    • A.O.U. Policlinico Università degli Studi di Napoli "Federico II"
  • Reggio Calabria, Italy, 89124
    • Dipartimento di ematologia
  • Roma, Italy, 00144
    • ASL Roma 2 - Ospedale Sant'Eugenio
  • CT
    • Catania, CT, Italy, 95123
      • Azienda Ospedaliero-Universitaria "Policlinico - Vittorio Emanuele" - P.O. G. Rodolico
• Korea, Republic of
  • Anyang-si, Korea, Republic of, 14068
    • Hallym University Sacred Heart Hospital
  • Busan, Korea, Republic of, 49201
    • Dong A University Hospital
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Hospital
  • Jeonju, Korea, Republic of, 54907
    • Chonbuk National University Hospital
  • Seoul, Korea, Republic of, 03181
    • Kangbuk Samsung Hospital
  • Seoul, Korea, Republic of, 06591
    • Seoul St. Mary's Hospital of the Catholic University of Korea
• Mexico
  • DF
    • Mexico City, DF, Mexico, 10700
      • Hospital Angeles del Pedregal (S.A. de C.V.)
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64000
      • Monterrey International Research Center
• Netherlands
  • Noord Holland
    • Amsterdam, Noord Holland, Netherlands, 1081 HV
      • VU University Medical Center
  • Noord-holland
    • Amsterdam, Noord-holland, Netherlands, 1081 BT
      • Klinische Farrnacologie en Apotheek
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital Department of Hematology
  • Trondheim, Norway, 7006
    • St. Olavs Hospital
• Poland
  • Chorzow, Poland, 41-500
    • SPZOZ ZSM w Chorzowie Oddzial Hematologiczny
  • Katowice, Poland, 40032
    • Samodzielny Publiczny Szpital Kliniczny im. A Mielęckiego, ŚUM w Katowicach
  • Kraków, Poland, 31501
    • Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Hematologii
  • Lublin, Poland, 20081
    • SPSK, Klinika Hematoonkologii i Transplantacji Szpiku w Lublinie
  • Wrocław, Poland, 50-367
    • Universytet Medyczny im. Piastów Śląskich we Wrocławiu Katedra i
  • Łódź, Poland, 93510
    • Wojewódzki Szpital Specjalistyczny im M. Kopernika, Klinika Hematologii Uniwersytetu Medycznego
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-214
      • Klinika Hematologii i Transplantologii Uniwersyteckie Centrum Kliniczne
• Singapore
  • Singapore, Singapore, 169608
    • Singapore General Hospital
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
  • Singapore, Singapore, 119228
    • National University Hospital, Main Building
• Slovakia
  • Bratislava, Slovakia, 851 07
    • Univerzitná Nemocnica Bratislava-Nemocnica sv. Cyrila a Metoda
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
      • The Medical Oncology Centre of Rosebank
    • Pretoria, Gauteng, South Africa, 0002
      • Department of Medical Oncology, University of Pretoria and Steve Biko
    • Pretoria, Gauteng, South Africa, 0181
      • Groenkloof Life hospital.
  • Western CAPE
    • Cape Town, Western CAPE, South Africa, 7935
      • Department of Haematology
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clínic
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28007
    • Hospital Universitario Gregorio Marañon
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Toledo, Spain, 45004
    • Hospital Virgen De La Salud
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital (Universitari(o)) Germans Trias i Pujol
  • Málaga
    • Madrid, Málaga, Spain, 28006
      • Hospital Universitario La Princesa
• Sweden
  • Linköping, Sweden, SE-581 85
    • Linkoping University Hospital
  • Lund, Sweden, SE-221 85
    • Skåne University Hospital
  • Stockholm, Sweden, SE-171 76
    • Karolinska University Hospital Solna
  • Umeå, Sweden, SE-901 85
    • Norrlands University Hospital
  • Uppsala, Sweden, SE-751 85
    • Akademiska hospital
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • R.o.c.
    • Taichung city, R.o.c., Taiwan, 40447
      • China Medical University Hospital
    • Tainan City, R.o.c., Taiwan, 710
      • Chi-Mei Medical Center
    • Taipei City, R.o.c., Taiwan, 10449
      • Mackay Memorial Hospital
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital
  • Bangkok, Thailand, 10700
    • Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital
  • Chiang MAI
    • Muang, Chiang MAI, Thailand, 50200
      • Division of Hematology, Department of Internal Medicine, Maharaj Nakorn Chiang Mai Hospital
• Ukraine
  • Cherkasy, Ukraine, 18009
    • MI "Cherkasy Regional Oncological Dispensary " of Cherkasy Regional Council
  • Ivano-Frankivsk, Ukraine, 76008
    • Regional Clinical Hospital in Ivano-Frankivsk, Hematology Department
  • Khmelnytskyi, Ukraine, 29000
    • Khmelnytskyi Regional Hospital, Hematology Department
  • Kyiv, Ukraine, 03115
    • State Institution "National research center for radiation medicine of NAMS of Ukraine",
  • Kyiv, Ukraine, 03115
    • State Institution "National research center for radiation medicine of NAMS of Ukraine"
  • Kyiv, Ukraine, 03115
    • transplantation department of hemotology and transplantology division within Clinical Radiology
  • Kyiv, Ukraine, 04112
    • Chair of internal medicine #2.
  • Kyiv, Ukraine, 04112
    • Kyiv City Clinical Hospital #9, Hematology department #1,
  • Lviv, Ukraine, 79044
    • State Institution "Institute of Blood Pathology and Transfusion Medicine NAMS of Ukraine"
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • Department of Haematology
  • Leicester, United Kingdom, LE1 5WW
    • The Hope Clinical Trials Facility
  • Greater London
    • London, Greater London, United Kingdom, W12 0HS
      • Catherine Lewis Centre, Hammersmith Hospital
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L7 8XP
      • Linda McCartney Centre
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Department of Clinical Haematology
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Cancer & Haematology Centre, Churchill Hospital
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Department of Haematology The Royal Hallamshire Hospital
  • WEST Midlands
    • Birmingham, WEST Midlands, United Kingdom, B9 5SS
      • Heartlands Hospital
  • WEST Yorkshire
    • Leeds, WEST Yorkshire, United Kingdom, LS9 7TF
      • St James's Institute of Oncology
• United States
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
  • Hawaii
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Permanente Hawaii
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center, Cancer Care Center
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Caldwell Cancer Care Center
    • Nampa, Idaho, United States, 83686
      • Saint Alphonsus Medical Center Nampa
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Cancer Center
    • Chicago, Illinois, United States, 60621
      • John H. Stroger, Jr. Hospital of Cook County
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood and Marrow Transplantation
    • Indianapolis, Indiana, United States, 46237
      • PHARMACY Department Franciscan St. Francis Health ATTN:Jill Leslie, Pharm D
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Cancer Center of Acadiana at Lafayette General Medical Center
    • Lafayette, Louisiana, United States, 70503
      • Lafayette General Medical Center
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center-Shreveport
    • Shreveport, Louisiana, United States, 71103
      • University Health Shreveport
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Rcca Md Llc
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center, ONC/Research Pharmacy
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital - Inpatient Pharmacy
    • Brighton, Michigan, United States, 48114
      • St. Joseph Mercy-Brighton
    • Canton, Michigan, United States, 48188
      • St. Joseph Mercy-Canton
    • Chelsea, Michigan, United States, 48118-1370
      • Chelsea Community Hospital
    • Detroit, Michigan, United States, 48236
      • St. John Hospital&Medical Center
    • Grosse Pointe Woods, Michigan, United States, 48236
      • St. John Hospital&Medical Center-Van Elslander Cancer Center
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center, Pharmacy
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Minnesota Oncology Hematology, Pa
    • Saint Louis Park, Minnesota, United States, 55426
      • Park Nicollet Frauenshuh Cancer Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Center Hematology and Oncology Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • San Juan Oncology Associates
  • New York
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital - Oncology / Hematology department
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital - Pharmacy Department
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14642
      • University of Rochester Investigational Drug Pharmacy
  • North Carolina
    • Pinehurst, North Carolina, United States, 28374
      • Firsthealth Moore Regional Hospital
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth Outpatient Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • West Chester, Ohio, United States, 45069
      • UC Health Physicians Office South,
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC University Hospital
    • Charleston, South Carolina, United States, 29425
      • MUSC University of South Carolina, Investigational Drug Services
    • Charleston, South Carolina, United States, 29425
      • MUSC-Hollings Cancer Center
    • Easley, South Carolina, United States, 29640
      • GHS Cancer Institute
    • Greenville, South Carolina, United States, 29615
      • GHS Cancer Institute
    • Greenville, South Carolina, United States, 29605
      • GHS Cancer Institute
    • Greer, South Carolina, United States, 29650
      • GHS Cancer Institute
    • Seneca, South Carolina, United States, 29672
      • GHS Cancer Institute
    • Spartanburg, South Carolina, United States, 29307
      • GHS Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson Cancer Center
  • Utah
    • Murray, Utah, United States, 84157
      • Utah Cancer Specialists
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • HSHS St. Vincent Hospital
    • Green Bay, Wisconsin, United States, 54301
      • HSHS St. Vincent Hospital Regional Cancer Center at HSHS St. Vincent Hospital
    • Green Bay, Wisconsin, United States, 54303
      • HSHS St. Vincent Hospital Regional Cancer Center at HSHS St. Mary's Hospital Medical Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Molecular diagnosis of CP CML of ≤ 6 months (from initial diagnosis).
2. Adequate hepatic, renal and pancreatic function.
3. Age ≥ 18 years.

Exclusion Criteria:

1. Any prior medical treatment for CML, including tyrosine kinase inhibitors (TKIs), with the exception of hydroxyurea and/or anagrelide treatment, which are permitted for up to 6 months prior to study entry (signature of ICF) if suitably approved for use in the subject's region.
2. Any past or current Central Nervous System (CNS) involvement, including leptomeningeal leukemia.
3. Extramedullary disease only.
4. Major surgery or radiotherapy within 14 days of randomization.
5. History of clinically significant or uncontrolled cardiac disease.
6. Known seropositivity to human immunodeficiency virus (HIV), current acute or chronic hepatitis B (hepatitis B surface-antigen positive), hepatitis C, cirrhosis or evidence of decompensated liver disease. Patients with resolved Hepatitis B can be included.
7. Recent or ongoing clinically significant GI disorder, e.g. Crohn's Disease, Ulcerative Colitis, or prior total or partial gastrectomy.
8. History of another malignancy within 5 years with the exception of basal cell carcinoma or cervical carcinoma in situ or stage 1 or 2 cancer that is considered adequately treated and currently in complete remission for at least l2 months.
9. Current, or recent (within 30 days, or 5 half-lives of investigational product) participation in other clinical trials of investigational agents and/or containing interventional procedures deemed contrary to the objectives and conduct of this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bosutinib; Bosutinib, 400 mg, oral administration once a day	Drug: Bosutinib; Bosutinib (Bosulif®) is an orally bioavailable, potent, multi-targeted, dual Src-Abl tyrosine kinase inhibitor (TKI) that has been approved for the treatment of adult patients with Philadelphia positive (Ph+) chronic phase (CP), accelerated phase (AP) and blast phase (BP) chronic myelogenous leukemia (CML) previously treated with other TKI inhibitor therapy.[1] This study will investigate the use of bosutinib as first-line treatment for patients with Ph+ CP CML.
Active Comparator: Imatinib; Imatinib, 400 mg, oral administration once a day	Drug: Imatinib; Imatinib mesylate (referred to in this protocol as imatinib) is an inhibitor of the BCR-ABL kinase and been the standard first-line therapy for patients with chronic-phase CML. Imatinib was granted approval by the European Commission in November 2001 and by the FDA in December 2002 for the treatment of newly diagnosed patients with CP Ph+ CML based on results from the IRIS trial. Imatinib is considered the standard of care for both first-line and later line settings, and consequently is an appropriate active comparator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Major Molecular Response (MMR) at Month 12	MMR was defined as a ratio of breakpoint cluster region to abelson (BCR-ABL/ABL) less than or equal to (<=) 0.1 percent (%) on the international scale (IS) (greater than or equal to [>=] 3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts [>=3000 ABL required]) by quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). The percentage of participants with MMR at Month 12 are reported.	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Major Molecular Response (MMR) Up to Month 18	MMR was defined as a ratio of BCR-ABL/ABL <=0.1% on the international scale (>=3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts [>=3000 ABL required]) by quantitative RT-qPCR. The percentage of participants with MMR for up to Month 18 are reported.	Up to Month 18
Kaplan-Meier Estimate of Probability of Retaining Major Molecular Response (MMR) at Month 48	The Kaplan-Meier curve was generated based on the first date of MMR until the date of the confirmed loss of MMR or censoring, objectively documented, for responders only. Confirmed loss of MMR was BCR-ABL/ABL IS ratio >0.1% in association with a >=5-fold increase in BCR-ABL/ABL IS ratio from the lowest value achieved up to that time-point confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, progressive disease (PD) or death due to PD within 28 days of last dose were considered confirmed loss of MMR. PD was defined as disease progression to accelerated phase (AP) or blast phase (BP) CML.	Month 48
Percentage of Participants With Complete Cytogenetic Response (CCyR) Up to Month 12	Complete Cytogenetic Response (CCyR) was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow (BM) aspirate. CCyR was achieved when there was 0% Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. The percentage of participants with CCyR for up to Month 12 are reported.	Up to Month 12
Kaplan-Meier Estimate of Probability of Retaining Complete Cytogenetic Response (CCyR) at Month 48	The Kaplan-Meier curve was generated based on the first date of CCyR until the date of the confirmed loss of CCyR or censoring, objectively documented, for responders only. Confirmed loss of CCyR was the presence of at least one Ph+ metaphase confirmed by a second assessment at least 28 days later. Treatment discontinuation due to suboptimal response/treatment failure, PD or death due to PD within 28 days of last dose were considered confirmed loss of CCyR. PD was defined as disease progression to AP or BP CML.	Month 48
Cumulative Incidence of Event Free Survival (EFS) Events	EFS was defined as time from randomization to death due to any cause, transformation to AP or BP at any time, confirmed loss of complete hematologic response (CHR), confirmed loss of CCyR or censoring. Loss of CHR was defined as a hematologic assessment of non-CHR (chronic phase, AP, or BP) confirmed by 2 assessments at least 4 weeks apart. Loss of CHR was defined as appearance of any of the following: WBC count that rises to >20.0*10^9/L, platelet count rises to >=600*10^9/L, appearance of palpable spleen or other extramedullary involvement proven by biopsy, appearance of 5% myelocytes in peripheral blood, appearance of blasts or promyelocytes in peripheral blood. Loss of CCyR was defined as at least 1 Ph+ metaphase from analysis of <100 metaphases confirmed by follow up cytogenetic analysis after 1 month. Cumulative incidence of EFS was defined as percentage of participants with EFS event at Month 60 and was adjusted for competing risk of treatment discontinuation without event.	Up to Month 60
Overall Survival (OS) Rate	OS was defined as the time (in months) from randomization to the occurrence of death due to any cause or censoring. Kaplan-meier analysis was used for determination of OS. Percentage of participants who were alive were estimated in this outcome measure.	Up to Month 60

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Trough Plasma Concentration by Complete Cytogenetic Response (CCyR) of Bosutinib	CCyR was based on the prevalence of Ph+ metaphases among cells in metaphase on a BM aspirate. CCyR was achieved when there was 0% Ph+ metaphases among cells in a BM sample when at least 20 metaphases from a BM sample were analyzed, or MMR if no BM was available. Trough plasma concentration of participants who had CCyR are presented in this outcome measure.	Pre-dose on Days 28, 56 and 84
Summary of Trough Plasma Concentration by Major Molecular Response (MMR) of Bosutinib	MMR was defined as a ratio of BCR-ABL/ABL <=0.1% on the international scale (>=3 log reduction from standardized baseline in ratio of BCR-ABL to ABL transcripts) by quantitative RT-qPCR. Trough plasma concentration of participants who had MMR are presented in this outcome measure.	Pre-dose on Days 28, 56 and 84
Summary of Trough Plasma Concentration by Presence of Grade 1 or Higher Adverse Events (AEs) of Bosutinib	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1= mild; Grade 2= moderate; within normal limits, Grade 3= severe or medically significant but not immediately life-threatening; Grade 4= life-threatening or disabling; urgent intervention indicated; Grade 5= death. Trough plasma concentration of participants who had grade 1 or higher AE are presented in this outcome measure. Data of plasma concentration is reported separately for each preferred term of AE.	Pre-dose on Days 28, 56 and 84
Summary of Trough Plasma Concentration by Presence of Grade 3 or Higher Adverse Events (AEs) of Bosutinib	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on NCI CTCAE version 4.0. Grade 1= mild; Grade 2= moderate; within normal limits, Grade 3= severe or medically significant but not immediately life-threatening; Grade 4= life-threatening or disabling; urgent intervention indicated; Grade 5= death. Trough plasma concentration of participants who had grade 3 or higher AE are presented in this outcome measure. Data of plasma concentration is reported separately for each preferred term of AE.	Pre-dose on Days 28, 56 and 84
Number of Participants With Vital Signs Abnormalities	Criteria for vital signs abnormalities: systolic blood pressure <80 millimeter of mercury (mmHg), >210 mmHg; diastolic blood pressure <40 mmHg, >130 mmHg; heart rate <40 beats per minute (bpm), >150 bpm; temperature <32 degree celsius, >40 degree celsius; weight >=10% increase from baseline, >=10% decrease from baseline. The number of participants with any vital sign abnormalities during On-treatment period are reported. On-Treatment was defined as values collected after the date of the first dose of test article until the last date of test article +28 days.	Baseline up to end of treatment (up to Month 60)
Number of Participants With Laboratory Test Abnormalities Based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 4.03	Laboratory parameters included hematological (haemoglobin, lymphocytes [absolute], neutrophils [absolute], platelets and leukocytes) and biochemistry (albumin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, amylase, bilirubin, creatinine kinase, calcium, creatinine, glucose, potassium, lipase, magnesium, phosphate, sodium, urate) parameters. Abnormalities in laboratory tests were graded by NCI CTCAE version 4.03 as Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. The number of participants with laboratory test abnormalities were reported.	Baseline up to end of treatment (up to Month 60)
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities	Criteria for ECG abnormalities included heart rate: increase of >15 bpm from baseline value and >=120 bpm, decrease of >15 bpm from baseline value and <=45 bpm; PR interval: change of >=20 msec from baseline value and >=220 milliseconds (msec); QRS interval >=120 msec; QTcB interval >500 msec, increase of >60 msec from baseline; >450 msec (Men) or >470 msec (Women). QT interval using Fridericia's correction (QTcF) >500 msec, increase of >60 msec from baseline, >450 msec (Men) or >470 msec (Women). The number of participants with ECG abnormalities during On-treatment period are reported. On-Treatment was defined as values collected after the date of the first dose of test article up until the last date of test article +28 days.	Baseline up to end of treatment (up to Month 60)
Number of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.	Baseline up to end of treatment (up to Month 60)
Number of Participants With Treatment-Emergent Adverse Events by National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) (Version 4.0)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on NCI CTCAE version 4.0. Grade 1 =mild; Grade 2 =moderate; Grade 3 =severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4 =life-threatening or disabling, urgent intervention indicated; Grade 5 =death. Treatment-emergent events were events between first dose of study drug and up to 60 months that were absent before treatment that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 adverse event, only the maximum CTCAE was reported.	Baseline up to end of treatment (up to Month 60)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Takahashi N, Cortes JE, Sakaida E, Ishizawa K, Ono T, Doki N, Matsumura I, Garcia-Gutierrez V, Rosti G, Ono C, Ohkura M, Tanetsugu Y, Viqueira A, Brummendorf TH. Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia: a pooled analysis. Int J Hematol. 2022 Jun;115(6):838-851. doi: 10.1007/s12185-022-03314-y. Epub 2022 Mar 2.
• Brummendorf TH, Cortes JE, Milojkovic D, Gambacorti-Passerini C, Clark RE, le Coutre P, Garcia-Gutierrez V, Chuah C, Kota V, Lipton JH, Rousselot P, Mauro MJ, Hochhaus A, Hurtado Monroy R, Leip E, Purcell S, Yver A, Viqueira A, Deininger MW; BFORE study investigators. Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial. Leukemia. 2022 Jul;36(7):1825-1833. doi: 10.1038/s41375-022-01589-y. Epub 2022 May 28.
• Chuah C, Koh LP, Numbenjapon T, Zang DY, Ong KH, Do YR, Ohkura M, Ono C, Viqueira A, Cortes JE, Brummendorf TH. Efficacy and safety of bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia in the Asian subpopulation of the phase 3 BFORE trial. Int J Hematol. 2021 Jul;114(1):65-78. doi: 10.1007/s12185-021-03144-4. Epub 2021 Apr 13.
• Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, Dyagil I, Glushko N, Milojkovic D, le Coutre P, Garcia-Gutierrez V, Reilly L, Jeynes-Ellis A, Leip E, Bardy-Bouxin N, Hochhaus A, Brummendorf TH. Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol. 2018 Jan 20;36(3):231-237. doi: 10.1200/JCO.2017.74.7162. Epub 2017 Nov 1.

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2014
• Primary Completion (Actual): August 11, 2016
• Study Completion (Actual): April 17, 2020

Study Registration Dates

• First Submitted: May 1, 2014
• First Submitted That Met QC Criteria: May 2, 2014
• First Posted (Estimate): May 5, 2014

Study Record Updates

• Last Update Posted (Actual): May 18, 2021
• Last Update Submitted That Met QC Criteria: April 16, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Pathologic Processes; Leukemia; Hematologic Diseases; Chronic; Imatinib; Bone Marrow Diseases; Pharmacologic Actions; Bosutinib; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Therapeutic Uses; Neoplasms by Histologic Type; Philadelphia Chromosome; Leukemia, Myeloid; Molecular Mechanisms of Pharmacological Action; BCR-ABL Positive; Myelogenous; Translocation, Genetic
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: AV001; 2013-005101-31 (EudraCT Number); B1871053 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No